3D Breast Tumor Models for Radiobiology Applications

Ravichandran, Akhilandeshwari; Clegg, Julien; Adams, Mark N.; Hampson, Madison; Fielding, Andrew; Bray, Laura J.

doi:10.3390/cancers13225714

Cited by 5 publications

(9 citation statements)

References 148 publications

(192 reference statements)

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“…Although 3D models, such as spheroids, have proven to be a tool to bridge the gap between 2D and in vivo models in precision medicine [ 10 ], in the radiobiology field, data comparing 3D in vitro models to in vivo models are limited. Hence, we assessed whether we could recapitulate the RT response seen in 3D spheroids ( Figure 2 A,B) in vivo by comparing the growth curves of HPV-negative CAL27 and HPV-positive SCC154 spheroids with in vivo tumor growth curves of the same cell lines ( Figure 3 B).…”

Section: Resultsmentioning

confidence: 99%

“…Preclinical models resembling human tumors are essential to understand the biological mechanisms of cancer formation and therapy response. In the field of radiation biology, clonogenic radiation survival curves, in which the number of surviving clones are measured, are the gold standard to determine the relative radiosensitivity of cells or to determine the effect of drug treatments [ 10 ]. This is because clonogenic survival assays are an efficient, practical and low-cost model [ 11 , 12 , 13 , 14 ].…”

Section: Introductionmentioning

confidence: 99%

“…Sharing the simplicity and efficiency of 2D cultures, 3D models more accurately represent the dynamic tumoral architecture, including typical features such as naturally occurring hypoxic regions and cell–cell interactions [ 13 , 16 ]. Although these features are important factors in determining the RT response, the use of 3D models in the field of radiobiology is still limited [ 10 ].…”

Section: Introductionmentioning

confidence: 99%

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Use of 3D Spheroid Models for the Assessment of RT Response in Head and Neck Cancer

Wegge

Dok

Dubois

et al. 2023

IJMS

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Radiotherapy (RT) is a key player in the treatment of head and neck cancer (HNC). The RT response, however, is variable and influenced by multiple tumoral and tumor microenvironmental factors, such as human papillomavirus (HPV) infections and hypoxia. To investigate the biological mechanisms behind these variable responses, preclinical models are crucial. Up till now, 2D clonogenic and in vivo assays have remained the gold standard, although the popularity of 3D models is rising. In this study, we investigate the use of 3D spheroid models as a preclinical tool for radiobiological research by comparing the RT response of two HPV-positive and two HPV-negative HNC spheroid models to the RT response of their corresponding 2D and in vivo models. We demonstrate that HPV-positive spheroids keep their higher intrinsic radiosensitivity when compared to HPV-negative spheroids. A good correlation is found in the RT response between HPV-positive SCC154 and HPV-negative CAL27 spheroids and their respective xenografts. In addition, 3D spheroids are able to capture the heterogeneity of RT responses within HPV-positive and HPV-negative models. Moreover, we demonstrate the potential use of 3D spheroids in the study of the mechanisms underlying these RT responses in a spatial manner by whole-mount Ki-67 and pimonidazole staining. Overall, our results show that 3D spheroids are a promising model to assess the RT response in HNC.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Use of 3D Spheroid Models for the Assessment of RT Response in Head and Neck Cancer

Wegge

Dok

Dubois

et al. 2023

IJMS

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“…[120][121][122] Organs-on-a-chip are versatile in vitro tools to recapitulate the structure and behavior of different tissues, that can easily be integrated into radiobiological studies. 22,23,25,120,123,124 For example, one group investigated the radiation response of different tissues, including the gut and bone-marrow, on chip (Fig. 4B).…”

Section: Radiobiology-on-chipmentioning

confidence: 99%

Radiotherapy on-chip: microfluidics for translational radiation oncology

et al. 2022

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“…Therefore, several new 3D breast cancer models have started to be used widely in different experiments [32,33]. These models highlight changes in cell behaviour between cancer cell growth in 2D and 3D models, including altered proliferation, gene expression, and chemo-and radiosensitivity [34,35]. Therefore, the goal of 3D models is to retain cellular behaviour as closely as possible to that of in vivo tissues and simultaneously preserve investigational possibilities, studying signalling alterations and tumour development with regard to drug responsiveness in particular.…”

Section: Introductionmentioning

confidence: 99%

Characterisation of 3D Bioprinted Human Breast Cancer Model for In Vitro Drug and Metabolic Targeting

Dankó

Petővári

Raffay

et al. 2022

IJMS

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Monolayer cultures, the less standard three-dimensional (3D) culturing systems, and xenografts are the main tools used in current basic and drug development studies of cancer research. The aim of biofabrication is to design and construct a more representative in vivo 3D environment, replacing two-dimensional (2D) cell cultures. Here, we aim to provide a complex comparative analysis of 2D and 3D spheroid culturing, and 3D bioprinted and xenografted breast cancer models. We established a protocol to produce alginate-based hydrogel bioink for 3D bioprinting and the long-term culturing of tumour cells in vitro. Cell proliferation and tumourigenicity were assessed with various tests. Additionally, the results of rapamycin, doxycycline and doxorubicin monotreatments and combinations were also compared. The sensitivity and protein expression profile of 3D bioprinted tissue-mimetic scaffolds showed the highest similarity to the less drug-sensitive xenograft models. Several metabolic protein expressions were examined, and the in situ tissue heterogeneity representing the characteristics of human breast cancers was also verified in 3D bioprinted and cultured tissue-mimetic structures. Our results provide additional steps in the direction of representing in vivo 3D situations in in vitro studies. Future use of these models could help to reduce the number of animal experiments and increase the success rate of clinical phase trials.

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3D Breast Tumor Models for Radiobiology Applications

Cited by 5 publications

References 148 publications

Use of 3D Spheroid Models for the Assessment of RT Response in Head and Neck Cancer

Use of 3D Spheroid Models for the Assessment of RT Response in Head and Neck Cancer

Radiotherapy on-chip: microfluidics for translational radiation oncology

Characterisation of 3D Bioprinted Human Breast Cancer Model for In Vitro Drug and Metabolic Targeting

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